Interactions among genetic loci are being appreciated increasingly in complex human diseases (Jung and others 2009). Recent examples of diseases or conditions associated with gene–gene interaction include coronary artery disease (Tsai and others 2007), type 2 diabetes (Qi and others 2007), Alzheimer’s disease (Fontalba and others 2009), schizophrenia (Gupta and others 2009), breast cancer (Briollais and others 2007), cervical cancer (Guzman and others 2008), autistic disorder (Ma and others 2009), and smoking addiction (Li and others 2008a; Tang and others 2009), to name a few. Interactive effects among genetic loci may exist without a significant main effect of any of them; in such cases, important genetic effects would have been missed if polymorphisms of such loci had not been modeled jointly (Jung and others 2009). Furthermore, in many cases, interactive effects of multiple genetic loci could be larger than the main effects at the individual loci (Robson and others 2004; Rodriguez and others 2006; Williams and others 2000).
